The global molecular epidemiology of human immunodeficiency virus Infection type 1 (HIV-1) is being studied by many groups worldwide. Phylogenetic analyses of HIV-1 sequences obtained from many countries have revealed eight distinctive phylogenetic subtypes among the isolates within the major "M" group. These eight subtypes, named A through H, have many important implications regarding the global evolution of HIV-1, the immunological aspects of HIV-1 infection, and future vaccine development. Searching for new HIV-1 subtypes in new locales is important since it will lead to a better understanding of HIV-1 natural evolution and its antigenic variation. The overall objective of this project is to help establish a new international center in Greece and Cyprus for the study of HIV variation and to study the molecular epidemiology in these two countries. In preliminary studies, we studied the genetic variation of HIV-1 isolates from twenty five patients in Cyprus by using the heteroduplex mobility assay (HMA) and DNA sequencing and we identified a new subtype I, within the M group. Epidemiological information obtained from the patients infected with the new HIV-1 subtype links the infection with the intravenous drug user community in Athens, Greece. All experimental procedures and molecular phylogenetic computer analysis proposed in this project will be direct expansions of our preliminary studies. All cloned HIV-1 env sequences obtained from patients in Cyprus will be used in HMA to search for similar and new strains, and selected isolates will be further analyzed by DNA sequencing and phylogenetic analysis. We anticipate to study about one hundred patients in Greece and about twenty five more patients in Cyprus within the first year of study. In the course of the study, all technical aspect-will be transferred to collaborators in Greece and Cyprus.